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Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow

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Abstract

Background

We have indicated previously that long-term feeding of beef tallow increases colorectal cancer in rats. In this study, we investigated the effects of conjugated linoleic acid (CLA) on colon carcinogenesis in rats under long-term feeding of beef tallow diets, pretreated with azoxymethane (AOM).

Methods

Six-week-old male Sprague–Dawley rats were fed with 10% beef tallow diet only, 10% beef tallow with 1% CLA in triglyceride form (CLA-TG), or 10% beef tallow with 1% CLA in free fatty acid form (CLA-FFA). Colon carcinogenesis was induced by two intraperitoneal injections of AOM. Aberrant crypt foci (ACFs) were examined at 12 weeks. Cancer, cell proliferation, apoptosis, Wnt signaling, and the arachidonic acid cascade were examined at 44 weeks.

Results

At 12 weeks, CLA-TG and CLA-FFA attenuated the increase in ACFs induced by 10% beef tallow and AOM pretreatment. At 44 weeks, both forms of CLA attenuated multiple colon cancers, and CLA-FFA reduced the incidence of colon cancer to 50% of that seen with CLA-TG. CLA-TG and CLA-FFA decreased the number of 5-bromo-2′-deoxyuridine-positive cells in AOM-pretreated rats fed with 10% beef tallow. CLA-FFA increased the number of apoptotic cells and the activity of caspase-3 in the colon mucosa, and CLA-TG enhanced the activity of caspase-3. Both forms of CLA suppressed Wnt signaling and the arachidonic acid cascade in rats treated with beef tallow and AOM.

Conclusion

These results suggested that CLA-TG and CLA-FFA suppressed colon carcinogenesis in rats with long-term feeding of a 10% beef tallow diet, through several mechanisms. The results of the present study with rats might be applicable to humans.

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Abbreviations

ACF:

Aberrant crypt foci

AOM:

Azoxymethane

BrdU:

5-Bromo-2′-deoxyuridine

CLA:

Conjugated linoleic acid

FFA:

Free fatty acid

TG:

Triglyceride

PGE2:

Prostaglandin E2

TXB2:

Thromboxane B2

COX-2:

Cyclooxygenase-2

NSAIDs:

Nonsteroidal anti-inflammatory drugs

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Acknowledgments

This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (KAKEN) 20590728 (K.F.), 20790499 (T.F.) and 20590745 (R.I.).

Conflict of interest statement

None.

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Authors and Affiliations

  1. Department of Internal Medicine and Gastrointestinal Endoscopy, Saga Medical School, 5-1-1 Nabeshima, Saga, 849-8501, Japan

    Ryosuke Shiraishi, Ryuichi Iwakiri, Takehiro Fujise, Tsukasa Kuroki, Takashi Kakimoto, Tooru Takashima, Yasuhisa Sakata, Seiji Tsunada & Kazuma Fujimoto

  2. Fujioka Hospital, Saga, 840-0201, Japan

    Yutaka Nakashima

  3. Department of Applied Biochemistry and Food Science, Saga University, Saga, 840-8502, Japan

    Teruyoshi Yanagita

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  1. Ryosuke Shiraishi
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Correspondence to Kazuma Fujimoto.

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Shiraishi, R., Iwakiri, R., Fujise, T. et al. Conjugated linoleic acid suppresses colon carcinogenesis in azoxymethane-pretreated rats with long-term feeding of diet containing beef tallow. J Gastroenterol 45, 625–635 (2010). https://doi.org/10.1007/s00535-010-0206-8

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